Control of the papillomavirus early-to-late switch by differentially expressed SRp20.
The viral early-to-late switch of papillomavirus infection is tightly linked to keratinocyte differentiation and is mediated in part by alternative mRNA splicing. Here, we report that SRp20, a cellular splicing factor, controls the early-to-late switch via interactions with A/C-rich RNA elements. An A/C-rich SE4 element regulates the selection of a bovine papillomavirus type 1 (BPV-1) late-specific splice site, and binding of SRp20 to SE4 suppresses this selection. Expression of late BPV-1 L1 or human papillomavirus (HPV) L1, the major capsid protein, inversely correlates with SRp20 levels in the terminally differentiated keratinocytes. In HPV type 16, a similar SRp20-interacting element also controls the viral early-to-late switch. Keratinocytes in raft cultures, which support L1 expression, make considerably less SRp20 than keratinocytes in monolayer cultures, which do not support L1 expression. Conversely, abundant SRp20 in cancer cells or undifferentiated keratinocytes is important for the expression of the viral early E6 and E7 by promoting the expression of cellular transcription factor SP1 for transactivation of viral early promoters.
Jia
Rong
R
HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, 10 Center Dr. 6N106, Bethesda, MD 20892-1868, USA.
Liu
Xuefeng
X
Tao
Mingfang
M
Kruhlak
Michael
M
Guo
Ming
M
Meyers
Craig
C
Baker
Carl C
CC
Zheng
Zhi-Ming
ZM
D052688:Bovine papillomavirus 1 / Q000502:physiology*; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D022821:RNA Splice Sites; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D014779:Virus Replication
D022821:RNA Splice Sites; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C491388:SRSF3 protein, human; D000068103:Serine-Arginine Splicing Factors